Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks the joints producing an inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, pericardium, pleura, and sclera, and also nodular lesions, most common in subcutaneous tissue under the skin. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a role in its chronicity and progression.
About 1% of the world's population is afflicted by rheumatoid arthritis, women three times more often than men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility. It is diagnosed chiefly on symptoms and signs, but also with blood tests (especially a test called rheumatoid factor) and X-rays. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in the diseases of joints and connective tissues (see, e.g., Majithia V, and Geraci S A (2007) Am. J. Med. 120 (11): 936-9; herein incorporated by reference in its entirety).
Current treatments for rheumatoid arthritis include: non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, gold therapy, methotrexate, tumor necrosis Factor Inhibitors such as etanercept (Enbrel®), adalimumab (Humira®), and infliximab (Remicade®), and other immunomodulatory and cytotoxic agents. While these treatments can be effective many require close supervision because of hazardous side effects. Response to treatment with these agents is variable and some patients still experience pain and joint degeneration. Thus, there is a need for additional compounds that can treat rheumatoid arthritis and related diseases.